Apparatus for separating discrete volumes of a composite liquid with balancing elements

ABSTRACT

An apparatus for separating at least two discrete volumes of a composite liquid into at least a first component and a second component comprises a centrifuge, with a rotor having a rotation axis comprising at least two separation cells, each for containing a separation bag containing a volume of composite liquid; and first balancing elements for balancing the rotor when the respective weights of the at least two separation bags in the at least two separation cells are different.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Application No.PCT/US2006/021827 filed Jun. 5, 2006 which claims the benefit of U.S.provisional Application No. 60/693,320 filed Jun. 22, 2005.

FIELD OF THE INVENTION

The present invention relates to an apparatus and a method forseparating at least two discrete volumes of a composite liquid into atleast two components.

BACKGROUND

The apparatus and a method of the invention are particularly appropriatefor the separation of biological fluids comprising an aqueous componentand one or more cellular components. For example, potential uses of theinvention include: extracting a plasma component and a cellularcomponent (including platelets, white blood cells, and red blood cells)from a volume of whole blood, the cellular component being subsequentlyfiltered so as to remove platelets and white blood cells from the redblood cells; extracting a plasma component, in which a substantialamount of platelets is suspended, and a red blood cell component from avolume of whole blood, the white blood cells being subsequently removedby filtration from the platelet component and the red blood cellcomponent; extracting a plasma component, a platelet component, and ared blood cell component from a volume of whole blood, the white bloodcells being subsequently removed by filtration from the plateletcomponent and the red blood cell component.

An apparatus for processing blood components is known from document WO03/089027. This apparatus comprises a centrifuge adapted to cooperatewith an annular separation bag connected to at least one product bag,e.g. a platelet component bag.

The centrifuge includes a rotor having a turntable for supporting theseparation bag, and a central compartment for containing the product bagconnected to the separation bag; and a squeezing system for squeezingthe separation bag and causing the transfer of a separated component(e.g. platelets suspended in plasma) from the separation bag into theproduct bag.

With this apparatus, a single discrete volume of blood is processed atonce.

An object of the present invention is to design a separation apparatusthat can process at once at least two discrete volumes of a compositeliquid, in particular discrete volumes that may be not the same, andwith the proportions of the various components of the composite liquidthat may vary from one discrete volume to another one.

According to the invention, a method for separating at least twodiscrete volumes of a composite liquid into at least a first componentand a second component comprises enclosing in at least two separationcells mounted on a rotor at least two separation bags containing twodiscrete volumes of a composite liquid respectively; storing in acontainer included in the rotor at least two first satellite bagsconnected to the at least two separation bags respectively; rotating therotor; and transferring a volume of hydraulic liquid into at least twointerconnected expandable hydraulic chambers located in the at least twoseparation cells respectively, whereby the hydraulic liquid getsdistributed under centrifugation forces in the at least twointerconnected hydraulic chambers so as to substantially balance therotor.

Other features of the method according to the invention are as follows:transferring a volume of hydraulic liquid into the at least twointerconnected hydraulic chambers comprises transferring a predeterminedvolume of hydraulic liquid; transferring a volume of hydraulic liquidinto the at least two interconnected hydraulic chambers comprisespumping hydraulic liquid into the at least two interconnected hydraulicchambers; transferring a volume of hydraulic liquid into the at leasttwo interconnected hydraulic chambers comprises connecting a source ofhydraulic liquid to the at least two interconnected hydraulic chambersso that a rotation of the rotor causes hydraulic liquid to betransferred from the source of hydraulic liquid into the at least twointerconnected hydraulic chambers; rotating the rotor comprises rotatingthe rotor at a sedimentation speed at which the at least first and asecond components sediment in each of the separation bags.

The method further comprises: transferring a first separated componentfrom the at least two separation bags into the at least two firstsatellite bags connected thereto respectively; and balancing anyunbalance of the rotor caused by the transfer of the first separatedcomponent into the at least two first satellite bags. Balancing anyunbalance of the rotor caused by the transfer of the first separatedcomponent into the at least two first satellite component bags comprisesrespectively storing the at least two first satellite bags in thecontainer against at least two interconnected flexible pouchescontaining a volume of a liquid secured to a wall of the container,whereby the at least two first satellite bags press against the at leasttwo pouches under centrifugation forces and distribute the volume ofliquid in the at least two pouches so as to balance the rotor.Transferring a first separated component from the at least twoseparation bags into the at least two first satellite bags connectedthereto respectively comprises: squeezing the at least two separationbags within the at least two separation cells so as to cause a transferof at least one fraction of the first component into the at least twofirst satellite bags connected thereto; detecting a characteristic of acomponent at a first determined location in each separation bag;stopping transferring the at least one fraction of the first componentfrom each separation bag into the first satellite bag connected thereto,upon detection of the characteristic of a component at the firstdetermined location. The method further comprises changing a speed ofthe rotor after detecting a characteristic of a component at the firstdetermined location in the separation bag in which such detection occurslast. The method further comprises changing a speed of the rotor after apredetermined period of time after detecting a characteristic of acomponent at the first determined location in one of the at least twoseparation bags.

The method further comprises: transferring a second separated componentfrom the at least two separation bags into at least two second satellitebags connected thereto respectively; and balancing any unbalance of therotor caused by the transfer of the second separated component into theat least two second satellite bags. Balancing any unbalance of the rotorcaused by the transfer of the second separated component into the atleast two second satellite component bags comprises respectively storingthe at least two second satellite bags in the container against the atleast two interconnected flexible pouches containing a volume of aliquid secured to a wall of the container, whereby the at least twosecond satellite bags press against the at least two pouches undercentrifugation forces and distribute the volume of liquid in the atleast two pouches so as to balance the rotor. Transferring a secondseparated component from the at least two separation bags into the atleast two second satellite bags connected thereto respectivelycomprises: squeezing one of the at least two separation bags within oneof the at least two separation cells so as to cause a transfer of thesecond component into the second satellite bag connected thereto;detecting a characteristic of a component at a second determinedlocation in either the squeezed separation bag or a tube connecting thesqueezed separation bag to a second satellite bag; stopping squeezingthe squeezed separation bag upon detection of the characteristic of acomponent at the second determined location; and successively repeatingthe above steps with each separation bag of the at least two separationbags.

The method further comprises stopping rotating the rotor after detectinga characteristic of a component at the second determined location in theseparation bag or the tube connected thereto in which such detectionoccurs last.

The method further comprises stopping rotating the rotor after apredetermined period of time after detecting a characteristic of acomponent at the second determined location in one of the at least twoseparation bags or the tube connected thereto.

According to the invention, an apparatus for separating at least twodiscrete volumes of a composite liquid into at least a first componentand a second component comprises a centrifuge comprises: a rotor havinga rotation axis, comprising at least two separation cells, each forcontaining a separation bag containing a volume of composite liquid; anda first balancing means for balancing the rotor when the respectiveweights of the at least two separation bags in the at least twoseparation cells are different, comprising: at least two expandablehydraulic chambers within the at least two separation cellsrespectively, and the at least two hydraulic chambers are fluidlyinterconnected; a source of hydraulic liquid fluidly connected to the atleast two hydraulic chambers; and a liquid transferring means fortransferring a volume of hydraulic liquid from the hydraulic liquidsource into the at least two interconnected hydraulic chambers so as tosubstantially balance the rotor when two separation bags respectivelycontained in the at least two different separation cells have differentweights.

Other features of the apparatus according to the invention are asfollows: The apparatus according further comprises a control unitprogrammed for causing the liquid transferring means to transfer apredetermined volume of hydraulic liquid from the hydraulic liquidsource into the at least two interconnected hydraulic chambers, and thepredetermined volume of hydraulic liquid is selected so as tosubstantially balance the rotor whatever the weights of two separationbags respectively contained in the at least two different separationcells.

The liquid transferring means comprises a pumping means for pumping avolume of hydraulic fluid into the at least two interconnected hydraulicchambers.

The source of hydraulic liquid is fixed with respect to the rotor and isfluidly connected to the at least two hydraulic chambers through arotary seal.

The liquid transferring means comprises a motor for driving the rotor inrotation and the source of hydraulic liquid is fixed with respect to therotor, below the at least two separation cells, and is fluidly connectedto the hydraulic chambers through a rotary seal, whereby a rotation ofthe rotor causes the volume of hydraulic liquid to be transferred fromthe hydraulic liquid source into the hydraulic chambers.

The first balancing means further comprises a valve fitted on a conduitbetween the source of hydraulic liquid and the rotary seal, forcontrolling a transfer into the hydraulic chambers of a predeterminedvolume of hydraulic liquid for balancing the rotor.

The at least two hydraulic chambers are interconnected by a circularconduit centered on the rotation axis, and the circular conduit isconnected to each hydraulic chamber to an area thereof that is closer toa periphery of the rotor than to the rotation axis.

The liquid transferring means comprises a motor for driving the rotor inrotation, and the source of hydraulic liquid comprises a reservoir forhydraulic liquid that is mounted on the rotor and is so designed andfluidly connected to the at least two hydraulic chambers that a rotationof the rotor causes a transfer of hydraulic liquid from the reservoirinto the at least two hydraulic chambers.

The reservoir comprises a housing defining an internal volume that issymmetrical with respect to the rotation axis and a circular inner areathat is the farthest to the rotation axis, and the at least twohydraulic chambers are in fluid communication with this circular area ofthe reservoir.

The apparatus further comprises: a storage means included in the rotorfor storing at least two satellite bags respectively connected to atleast two separation bags contained in the at least two separationcells; and a component transferring means for transferring at least oneseparated component from each separation bag into a satellite bagconnected thereto.

The component transferring means comprises a pumping means for pumpinghydraulic liquid from the source of hydraulic liquid into the at leasttwo interconnected hydraulic chambers so as to squeeze the at least twoseparation bags within the at least two separation cells and to cause acomponent separated therein to flow into a satellite bag connected toeach separation bag.

The source of hydraulic liquid is fixed with respect to the rotor, belowthe at least two separation cells, and is fluidly connected to the atleast two hydraulic chambers through a rotary seal, and the componenttransferring means comprises: a motor for driving the rotor in rotation;and at least one valve member associated with each separation cell forselectively allowing or blocking a flow of fluid between a separationbag and a satellite bag, whereby a rotation of the rotor causeshydraulic liquid to be transferred from the hydraulic liquid source intothe at least two hydraulic chambers and to squeeze the at least twoseparation bags within the at least two separation cells, which causes acomponent separated in a separation bag to flow into a satellite bagconnected thereto when the valve member for allowing or blocking a flowof fluid between the separation bag and the satellite bag is open.

The source of hydraulic liquid comprises a reservoir for hydraulicliquid that is mounted on the rotor and is fluidly connected to the atleast two hydraulic chambers, and the component transferring meanscomprises: a motor for driving the rotor in rotation; and at least onevalve member associated with each separation cell for selectivelyallowing or blocking a flow of fluid between a separation bag and asatellite bag, whereby a rotation of the rotor causes hydraulic liquidto be transferred from the reservoir into the at least two hydraulicchambers and to squeeze the at least two separation bags within the atleast two separation cells, which causes a component separated in aseparation bag to flow into a satellite bag connected thereto when thevalve member for allowing or blocking a flow of fluid between theseparation bag and the satellite bag is open.

The apparatus further comprises a second balancing means for balancingthe rotor when the at least two satellite bags stored in the storingmeans cause an unbalance of the rotor.

The storage means comprises a central container around which the atleast two separation cells are symmetrically arranged with respect tothe rotation axis; and

The second balancing means comprises at least two interconnectedflexible pouches partially filled with a liquid, and the pouches arearranged against a wall of the central container so that the at leastone satellite bag connected to each separation bag presses onto a pouchduring centrifugation.

The storage means comprises a central container around which the atleast two separation cells are symmetrically arranged with respect tothe rotation axis; and the second balancing means comprises acylindrical flexible pouch partially filled with a liquid lining a wallof the central container so that the at least one satellite bagconnected to each separation bag presses onto the pouch duringcentrifugation.

The storage means comprises one container associated with eachseparation cell, the container being located between the separation celland the rotation axis; and the second balancing means comprises oneflexible pouch partially filled with a liquid arranged against a wall ofeach container so that a satellite bag stored in the container pressesonto a pouch during centrifugation, and a flexible pouch in onecontainer is fluidly interconnected with a pouch in another container.

The apparatus further comprises: a storage means included in the rotorfor storing at least two first satellite bags respectively connected toat least two separation bags contained in the at least two separationcells; and at least one valve member associated with each separationcell for selectively allowing or blocking a flow of fluid between aseparation bag and a first satellite bag, and the at least one valvemember is mounted on the rotor so as to be between the associatedseparation cell and the storage means, with respect to the rotationaxis.

The apparatus further comprises: a storage means included in the rotorfor storing at least two first satellite bags respectively connected toat least two separation bags contained in the at least two separationcells; and at least one valve member associated with each separationcell for selectively allowing or blocking a flow of fluid between aseparation bag and a first satellite bag, and the at least one valvemember is mounted on the rotor so that the storage means is between theat least one valve member and the associated separation cell, withrespect to the rotation axis.

The apparatus further comprises at least one sensor associated with eachseparation cell for generating information related to a characteristicof a component separated in a separation bag within the separation cell.

The at least one sensor is mounted on the rotor so as to detect acharacteristic of a component in a separation bag contained in theassociated separation cell.

The at least one sensor is mounted on the rotor so as to detect acharacteristic of a component in a tube connected to a separation bagcontained in the associated separation cell.

Each separation cell comprises a substantially closed cavity having alongitudinal axis intersecting the rotation axis of the rotor andcomprises a portion closer to the rotation axis of the rotor that isdefined by four walls converging towards the longitudinal axis of thecavity.

The longitudinal axis of the cavity of each separation cell intersectsthe rotation axis of the rotor at an acute angle.

Each separation cell comprises a cavity having a bottom wall, an upperwall and a lower wall, and the hydraulic chamber is underneath amembrane that is lining at least part of either the upper wall or thelower wall of the cavity.

Each separation cell comprises a cavity having a bottom wall, an upperwall, and a lower wall, and the hydraulic chamber comprising a flexiblepouch that rests at least on part the lower wall.

The density of the hydraulic liquid is so selected as to be higher thanthe density of the component having the highest density.

Each separation cell comprises a cavity having a bottom wall, an upperwall, and lower wall, and the hydraulic chamber is defined by an elasticsocket that is secured to the separation cell so as to extend betweenthe upper wall and the lower wall.

The density of the hydraulic liquid is so selected as to be between thedensity of a first component and the density of a second component.

Each separation cell comprises a securing means for securing an upperedge of a separation bag so that the upper edge is the portion of theseparation bag that is the closest to the rotation axis.

The apparatus further comprises: at least one sensor associated witheach separation cell for generating information related to acharacteristic of a component separated in a separation bag within theseparation cell; a memory unit for storing at least one change inrotation speed of the rotor; and a control unit programmed: forreceiving from the memory the at least one change in rotation speed, andinformation generated by the at least one sensor associated with eachseparation cell; and for causing the at least one change in rotationspeed in view of information generated by one of the at least one sensorassociated with each of the at least two separation cells.

The control unit is programmed for causing the at least one change ofrotation speed in view of information generated by the first of the atleast one sensor associated with the at least two separation cells thatdetects a characteristic of a component separated in a separation bagwithin a separation cell.

The control unit is programmed for causing the at least one change ofrotation speed in view of information generated by the last of the atleast one sensor associated with the at least two separation cells thatdetects a characteristic of a component separated in a separation bagwithin a separation cell.

The apparatus further comprises at least one valve member associatedwith each separation cell for selectively allowing or blocking a flow offluid between a separation bag within the separation cell and asatellite bag connected thereto, and the control unit is furtherprogrammed for causing at least once in a separation process the atleast one valve member associated with a separation cell to block a flowof fluid between a separation bag within the separation cell and asatellite bag connected thereto following a detection of thecharacteristic of a separated component by the at least one sensorassociated with the same separation cell.

The apparatus further comprises at least one valve member associatedwith each separation cell for selectively allowing or blocking a flow offluid between a separation bag within the separation cell and asatellite bag connected thereto, and the control unit is furtherprogrammed for causing at least once in a separation process the atleast one valve member associated with a separation cell to allow a flowof fluid between a separation bag within the separation cell and asatellite bag connected thereto following a detection of thecharacteristic of a separated component by the at least one sensorassociated with another separation cell.

The apparatus further comprises at least one valve member associatedwith each separation cell for selectively allowing or blocking a flow offluid between a separation bag within the separation cell and asatellite bag connected thereto, and the control unit is furtherprogrammed for: causing the rotor to rotate at a sedimentation speed forseparating a least two components in at least two separation bagscontained in the at least two separation cell respectively; causing theleast one valve member associated with each separation cell to allow aflow of fluid between each separation bag and the satellite bagconnected thereto; causing the component transferring means to transferat least a portion of a separated component from each of the at leasttwo separation bags into the satellite bag connected thereto; causingthe least one valve member associated with each separation cell to blocka flow of fluid between the separation bag within the separation celland the satellite bag connected thereto, when the sensor associated withthe separation cell detects the characteristic of a separated component.

The control unit is further programmed for: causing the componenttransferring means to stop transferring a separated component from theat least two separation bags into the satellite bags connected theretowhen one sensor associated with one of the at least two the separationcells detects the characteristic of a separated component; causing thecomponent transferring means to transfer a separated component from theat least two separation bags into the satellite bags connected thereto,after the valve member associated with the separation cell associatedwith the sensor that has detected the characteristic of a separatedcomponent has blocked a flow of fluid between the separation bag and thesatellite bag connected thereto.

The at least one sensor comprises a first sensor for detecting acharacteristic of a separated component in a separation bag within aseparation cell; the least one valve member comprises a first valvemember for allowing or blocking a flow of fluid between a separation bagand a first satellite bag connected thereto; the control unit is furtherprogrammed for controlling an actuation of the first valve member inview of information from the first sensor.

The at least one sensor comprises a second sensor for detecting acharacteristic of a separated component in a tube connecting aseparation bag to a second satellite bag; the least one valve membercomprises a second valve member for allowing or blocking a flow of fluidbetween a separation bag and a second satellite bag connected thereto;the control unit is further programmed for controlling an actuation of asecond valve member in view of information from the second sensor.

According to the invention, a set of bags for separating at least twodiscrete volumes of a composite liquid into at least a first componentand a second component comprises: a collection and separation bag havinga median axis, a top and a bottom, for cooperating with a centrifuge sothat the median axis of the collection and separation bag substantiallyintersects the rotation axis, the bottom is the farthest from therotation axis and the top is the closest to the rotation axis, and thetop of the separation bag comprises two edges converging towards a tiplocated on the median axis; a collection tube having a first endconnected to the collection and separation bag; and at least twosatellite bags connected to the top of the collection and separationbag, and at least one satellite bag in which a component is to betransferred during a rotation of the centrifuge, is connected to the tipof the collection and separation bag.

Other features of the set of bags according to the invention are asfollows: the set of bags further comprises: a first flexible tube havinga first end connected to a first satellite bag; a valve section forengaging a first pinch valve of the centrifuge; a second flexible tubehaving: a first end connected to a second satellite bag; a valve sectionfor engaging a second pinch valve of the centrifuge; and a three-wayconnector having: an inlet channel for connection to the collection andseparation bag; a first outlet channel connected to a second end of thefirst tube, and a second outlet channel connected to a second end of thesecond tube, and the three-way connector is so shaped as to allow asection of either one of the first outlet channel and the first tube anda section of either one of the second outlet channel and the second tubeto be the closest to the rotation axis when the first valve section isengaged in the first pinch valve and the second valve section is engagedin the second pinch valve.

The section of either one of the first outlet channel and the first tubeand the section of either one of the second outlet channel and thesecond tube that are the closest to the rotation axis when the firstvalve section is engaged in the first pinch valve and the second valvesection is engaged in the second pinch valve, coincide at a meetingpoint of the first outlet channel and the second outlet channel.

The first outlet channel and the second outlet channel are substantiallyaligned and the inlet channel is perpendicular thereto.

The section of either one of the first outlet channel and the first tubethat is the closest to the rotation axis when the first valve section isengaged in the first pinch valve and the second valve section is engagedin the second pinch valve comprises a section of the first tube betweenthe three way connector and the first valve section, and the section ofeither one of the second outlet channel and the second tube that is theclosest to the rotation axis when the first valve section is engaged inthe first pinch valve and the second valve section is engaged in thesecond pinch valve comprises a section of the second tube between thethree way connector and the second valve section.

An angle between the first outlet channel and the inlet channel isbetween 90 degrees and 180 degrees, and an angle between the secondoutlet channel and the inlet channel is between 90 degrees and 180degrees.

The inlet channel, the first outlet channel, and the second outletchannel join in a central location.

The first outlet channel connects to the inlet channel at a firstlocation and the second outlet channel connects to the inlet channel ata second location, the first location being closer to the rotation axisthan the second location when the first valve section is engaged in thefirst pinch valve and the second valve section is engaged in the secondpinch valve.

The bag set further comprises a third tube having a first end connectedto the tip of the collection and separation bag and a second endconnected to the inlet channel. The third tube comprises a detectionsection for engaging a cell detector of the centrifuge. The bag setfurther comprises a breakable stopper connected to the third tube.

The bag set is for the separation of whole blood into a plasmacomponent, a platelet component and a red blood cell component, and thefirst satellite bag is for collecting the plasma component and thesecond satellite bag is for collecting the platelet component.

The bag set further comprises: a third satellite bag for collecting redblood cells; a third tube having: a first section having a first endconnected to the top of the collection and separation bag; and a secondsection having a second end connected to the third satellite bag; and aleuko-reduction filter having an inlet connected to a second end of thefirst section of the third tube and an outlet connected to a first endof the second section of the third tube.

The bag set further comprises a needle connected to a second end of thecollection tube.

Other features and advantages of the invention will appear from thefollowing description and accompanying drawings, which are to beconsidered exemplary only.

BRIEF DESCRIPTION OF THE DRAWINGS

In the accompanying drawings:

FIG. 1 is a schematic view of a first set of bags designed forcooperating with a separation apparatus;

FIG. 2 is a schematic view of a second set of bags designed forcooperating with a separation apparatus;

FIGS. 3 a, 3 b are schematic views of two variants of a detail of theset of bags of FIG. 2;

FIG. 4 is a schematic view, partly in cross-section along a diametralplane, of a first embodiment of a separation apparatus;

FIG. 5 is a top view of the rotor of the separation apparatus of FIG. 4;

FIG. 6 is a perspective view of a first embodiment of a passivebalancing unit for a separation apparatus;

FIG. 7 is a perspective view of a second embodiment of a passivebalancing unit for a separation apparatus;

FIG. 8 is schematic view, in cross-section along a radial plane, of aseparation cell of the separation apparatus of FIGS. 4 and 5;

FIG. 9 is schematic view, in cross-section along a radial plane, of anembodiment of a separation cell adjacent to a storage container;

FIG. 10 is a perspective view of a rotor of a second embodiment of aseparation apparatus;

FIG. 11 is a cross-section view of the rotor of FIG. 10, along adiametral plane;

FIG. 12 is a top view of the rotor of FIG. 10;

FIG. 13 is a schematic view, in cross-section along a diametral plane,of a third embodiment of a separation apparatus;

FIG. 14 is schematic view, in cross-section along a radial plane, of aseparation cell of the separation apparatus of FIG. 13;

FIG. 15 is a perspective view of the flexible diaphragm of theseparation cell of FIG. 14;

FIGS. 16 to 18 are schematic views, in cross-section along a radialplane, of the separation cell FIG. 14 containing a separation bag atdifferent stages of a separation process; and

FIG. 19 is a schematic view, in cross-section along a diametral plane,of a fourth embodiment of a separation apparatus.

DESCRIPTION OF THE EMBODIMENTS

For the sake of clarity, the invention will be described with respect toa specific use, namely the separation of whole blood into at least twocomponents, in particular into a plasma component and a red blood cellcomponent, or into a plasma component, a platelet component and a redblood cell component. The discrete volume mentioned hereunder willtypically be the volume of a blood donation. The volume of a blooddonation may vary from one donor to another one (450 ml plus or minus10%). It is also recalled that the proportion of the components of bloodusually varies from one donor to another one, in particular thehematocrit, which is the ratio of the volume of the red blood cells tothe volume of the sample of whole blood considered. In other words thedensity of blood may slightly vary for one donor to another one. Itshould be understood however that this specific use is exemplary only.

FIG. 1 shows an example of a set of bags adapted to the separation of acomposite liquid (e.g. whole blood) into a first component (e.g. aplasma component containing or not a substantial amount of suspendedplatelets) and a second component (e.g. a blood cell component). Thisbag set comprises a flexible separation bag 1 and two flexible satellitebags 2, 3 connected thereto.

When the composite liquid is whole blood, the separation bag 1 has twopurposes, and is successively used as a collection bag and as aseparation bag. It is intended for initially receiving a discrete volumeof whole blood from a donor (usually about 450 ml) and to be used lateras a separation chamber in a separation apparatus. The separation bag 1is flat and generally rectangular. It is made of two rectangular sheetsof plastic material that are welded together so as to definetherebetween an interior space having a main rectangular portionconnected to a triangular top downstream portion. A first tube 4 isconnected to the tip of the triangular portion, and a second and a thirdtubes 5, 6 are connected to either lateral edges of the triangularportion, respectively. The proximal ends of the three tubes 4, 5, 6 areembedded between the two sheets of plastic material so as to beparallel. The separation bag 1 further comprises a hole 8 in each of itscorners that are adjacent to the three tubes 4, 5, 6. The holes 8 areused to secure the separation bag to a separation cell, as will bedescribed later.

The separation bag initially contains a volume of anti-coagulantsolution (typically about 63 ml of a solution of citrate phosphatedextrose for a blood donation of about 450 ml), and the first and thirdtubes 4, 6 are fitted at their proximal end with a breakable stopper 9,10 respectively, blocking a liquid flow therethrough.

The second tube 5 is a collection tube having a needle 12 connected toits distal end. At the beginning of a blood donation, the needle 12 isinserted in the vein of a donor and blood flows into the collection(separation) bag 1. After a desired volume of blood has been collectedin the collection (separation) bag 1, the collection tube 5 is sealedand cut.

The first satellite bag 2 is intended for receiving a plasma component.It is flat and substantially rectangular. It is connected to the distalend of the first tube 4.

The second satellite bag 3 is intended for receiving a red blood cellcomponent. It is flat and substantially rectangular. It is connected tothe distal end of the third tube 6. The third tube 6 comprises twosegments respectively connected to the inlet and the outlet of aleuko-reduction filter 13. The second satellite bag 3 contains a volumeof storage solution for red blood cells, and the third tube 6 is fittedat its distal end with a breakable stopper 14 blocking a liquid flowtherethrough.

FIG. 2 shows an example of a set of bags adapted to the separation of acomposite liquid (e.g. whole blood) into a first component (e.g. aplasma component), an intermediate component (e.g. a plateletcomponent), and a second component (e.g. a red blood cell component).This bag set comprises a flexible separation bag 1 and three flexiblesatellite bags 2, 3, 15 connected thereto.

This second set of bags differs from the set of bags of FIG. 1 in thatit comprises a third satellite bag 15, which is intended to receive aplatelet component, and a T-shaped three-way connector 16 having its legconnected by the first tube 4 to the separation bag 1, a first armconnected by a fourth tube 17 to the first satellite bag 2 (plasmacomponent bag), and a second arm connected by a fifth tube 18 to thethird satellite bag 15 (platelet component bag). Like the first andsecond satellite bags 2, 3, the third satellite bag 15 is flat andsubstantially rectangular.

FIGS. 3 a, 3 b show two variants of the T-shaped three-way connector 16of the bag set of FIG. 2.

The three-way connector 16 a shown in FIG. 3 a has the shape of aregular three-point star having a first outlet channel 21 and a secondoutlet channel 22 that are connected to an inlet channel 20 at an angleof about 120 degrees.

The three-way connector 16 b shown in FIG. 3 b, defines a first outletchannel 21 and a second outlet channel 22 that are perpendicularlyconnected to an inlet channel 20 and are offset along the inlet channel20 so that the first outlet channel 21 is further than the second outletchannel 22 from the end of the inlet channel 20 that is connected to thefirst tube 4.

The three-way connectors 16, 16 a, 16 b are arranged such that when theseparation bag of FIG. 2 (or any of its variants represented in FIGS. 3a, 3 b) is mounted in a separation apparatus (to be described in detailbelow), in which a separation cell for a separation bag 1, a storagecontainer for the satellite bags 2, 3, 15, and a first and second pinchvalve members for allowing or stopping a flow of liquid in the fourthand fifth tubes 17, 18 are arranged in this order along a radialdirection from a rotation axis of the separation apparatus, with thepinch valve members being the closest to the rotation axis. In thisparticular configuration, when the fourth and fifth tubes 16, 17 areengaged in the first and second pinch valve members as shown in FIGS. 2,3 a, 3 b, then the three-way connector 16, 16 b, or a bend in the fourthand fifth tubes 17, 18 in the case of the connector of FIG. 3 a, are theclosest portion(s) of the whole bag set to the rotation axis. Theresults of this disposition are that, when the separation apparatusrotates, any air in the bag set will gather in the connector in an areathat is the closest to the rotation axis (junction point of the threechannels 20, 21, 22 in the connectors shown in FIGS. 2, 3 b) or in thebends in the fourth and fifth tube 17, 18 between the connector and thepinch valve members 17, 18 when the connector used is the connector ofFIG. 3 a. This air buffer between the separation bag and the satellitebag will prevent any undesirable siphoning of contents of a satellitebag into the separation bag under centrifugation forces.

The three-way connector 16 b presents a particular interest when the bagset of FIG. 2 is used to separate a plasma component and a plateletcomponent. When the plasma component has been transferred into the firstsatellite bag 2 and the platelet component has been transferred into thethird satellite bag 15, the connector 16 b shown in FIG. 3 b allow forflushing the second channel 22, which may contain remaining platelets,with a small volume of plasma trapped in the fourth tube 17 between theconnector 16 b and the first pinch valve member.

FIGS. 4, 5, 6, 8 show a first embodiment of an apparatus forsimultaneously separating by centrifugation four discrete volumes of acomposite liquid. The apparatus comprises:

-   -   a centrifuge adapted to receive four of either set of bags shown        in FIGS. 1 and 2, with the four discrete volumes of a composite        liquid contained in the four separation bags;    -   a component transferring means for transferring at least one        separated component from each separation bag into a satellite        bag connected thereto;    -   a first balancing means for initially balancing the rotor when        the weights of the four separation bags are different; and    -   a second balancing means for balancing the rotor when the        weights of the separated components transferred into the        satellite bags cause an unbalance of the rotor.

The centrifuge comprises a rotor that is supported by a bearing assembly30 allowing the rotor to rotate around a rotation axis 31. The rotorcomprises:

-   -   a cylindrical rotor shaft 32 to which a pulley 33 is connected;    -   a storage means comprising a central cylindrical container 34        for containing satellite bags, which is connected to the rotor        shaft 32 at the upper end thereof so that the longitudinal axis        of the rotor shaft 32 and the longitudinal axis of the container        34 coincide with the rotation axis 31, and    -   a frusto-conical turntable 35 connected to the upper part of the        central container 34 so that its central axis coincides with the        rotation axis 31. The frusto-conical turntable 35 flares        underneath the opening of the container 34. Four identical        separation cells 40 are mounted on the turntable 35 so as to        form a symmetrical arrangement with respect to the rotation axis        31.

The centrifuge further comprises a motor 36 coupled to the rotor by abelt 37 engaged in a groove of the pulley 33 so as to rotate the rotorabout the rotation axis 31.

Each separation cell 40 comprises a container 41 having the generalshape of a rectangular parallelepiped. The separation cells 40 aremounted on the turntable 35 so that their respective median longitudinalaxes 42 intersect the rotation axis 31, so that they are locatedsubstantially at the same distance from the rotation axis 31, and sothat the angles between their median longitudinal axes 42 aresubstantially the same (i.e. 90 degrees). The exact position of theseparation cells 40 on the turntable 35 is adjusted so that the weighton the turntable is equally distributed when the separation cells 40 areempty, i.e. so that the rotor is balanced. It results from thearrangement of the separating cells 40 on the turntable 35 that theseparating cells 40 are inclined with respect to the rotation axis 31 ofan acute angle equal to the angle of the frustum of a cone thatgeometrically defines the turntable 35.

Each container 41 comprises a cavity 43 that is so shaped anddimensioned as to loosely accommodate a separation bag 1 full of liquid,of the type shown in FIGS. 1 and 2. The cavity 43 (which will bereferred to later also as the “separation compartment”) is defined by abottom wall, that is the farthest to the rotation axis 31, a lower wallthat is the closest to the turntable 35, an upper wall opposite to thelower wall, and two lateral walls. The cavity 43 comprises a main part,extending from the bottom wall, which has substantially the shape of arectangular parallelepiped with rounded angles, and an upper part, whichhas substantially the shape of a prism having convergent triangularbases. In other words, the upper part of the cavity 43 is defined by twocouples of opposite walls converging towards the central median axis 42of the cavity 43. One interest of this design is to cause a radialdilatation of the thin layer of a minor component of a composite fluid(e.g. the platelets in whole blood) after separation by centrifugation,and makes it more easily detectable in the upper part of a separationbag. The two couples of opposite walls of the upper part of theseparation cell 40 converge towards three cylindrical parallel channels44, 45, 46, opening at the top of the container 41, and in which, when aseparation bag 1 is set in the container 41, the three tubes 4, 5, 6extend.

The container 41 also comprises a hinged lateral lid 47, which iscomprised of an upper portion of the external wall of the container 41,i.e. the wall that is opposite to the turntable 35. The lid 47 is sodimensioned as to allow, when open, an easy loading of a separation bag1 full of liquid into the separation cell 40. The container 41 comprisesa fast locking means (not shown) by which the lid 47 can be locked tothe remaining part of the container 41.

The container 41 also comprises a securing means for securing aseparation bag 1 within the separation cell 40. The bag securing meanscomprises two pins 48 protruding on the internal surface of the lid 47,close to the top of separation cell 40, and two corresponding recesses49 in the upper part of the container 41. The two pins 48 are so spacedapart and dimensioned as to fit into the two holes 8 in the upper cornerof a separation bag 1.

The separation apparatus further comprises a component transferringmeans for transferring at least one separated component from eachseparation bag into a satellite bag connected thereto. The componenttransferring means comprises a squeezing system for squeezing theseparation bags 1 within the separation compartments 43 and causing thetransfer of separated components into satellite bags 2, 3, 15.

The squeezing system comprises a flexible diaphragm 50 that is securedto each container 41 so as to define an expandable chamber 51 in thecavity thereof. More specifically, the diaphragm 50 is dimensioned so asto line the bottom wall of the cavity 43 and a large portion of thelower wall of the cavity 43, which is the closest to the turntable 35.

The squeezing system further comprises a peripheral circular manifold 52that forms a ring within the turntable 35 extending close to theperiphery of the turntable 35. Each expansion chamber 51 is connected tothe manifold 52 by a supply channel 53 that extends through the wall ofthe respective container 41, close to the bottom thereof.

The squeezing system further comprises a hydraulic pumping station 60for pumping a hydraulic liquid in and out the expandable chambers 51within the separation cells 40. The hydraulic liquid is selected so asto have a density slightly higher than the density of the more dense ofthe components in the composite liquid to be separated (e.g. the redblood cells, when the composite liquid is blood). As a result, duringcentrifugation, the hydraulic liquid within the expandable chambers 51,whatever the volume thereof, will generally remain in the most externalpart of the separation cells 40. The pumping station 60 is connected tothe expandable chambers 51, through a rotary seal 69, by a duct 56 thatextends through the rotor shaft 32, the bottom and lateral wall of thecentral container 34, and, from the rim of the central container 34,radially through the turntable 35 where it connects to the manifold 52.

The pumping station 60 comprises a piston pump having a piston 61movable in a hydraulic cylinder 62 fluidly connected via a rotary fluidcoupling 63 to the rotor duct 54. The piston 61 is actuated by a steppermotor 64 that moves a lead screw 65 linked to the piston rod. Thehydraulic cylinder 62 is also connected to a hydraulic liquid reservoir66 having an access controlled by a valve 67 for selectively allowingthe introduction or the withdrawal of hydraulic liquid into and from ahydraulic circuit including the hydraulic cylinder 62, the rotor duct 56and the expandable hydraulic chambers 51. A pressure gauge 68 isconnected to the hydraulic circuit for measuring the hydraulic pressuretherein.

The separation apparatus further comprises four pairs of a first andsecond pinch valve members 70, 71 that are mounted on the rotor aroundthe opening of the central container 34. Each pair of pinch valvemembers 70, 71 faces one separation cell 40, with which it isassociated. The pinch valve members 70, 71 are designed for selectivelyblocking or allowing a flow of liquid through a flexible plastic tube,and selectively sealing and cutting a plastic tube. Each pinch valvemember 70, 71 comprises an elongated cylindrical body and a head havinga groove 72 that is defined by a stationary upper jaw and a lower jawmovable between an open and a closed position. The groove 72 is sodimensioned that one of the tubes 4, 17, 18 of the bag sets shown inFIGS. 1 and 2 can be snuggly engaged therein when the lower jaw is inthe open position. The elongated body contains a mechanism for movingthe lower jaw and it is connected to a radio frequency generator thatsupplies the energy necessary for sealing and cutting a plastic tube.The pinch valve members 70, 71 are mounted inside the central container34, adjacent the interior surface thereof, so that their longitudinalaxes are parallel to the rotation axis 31 and their heads protrude abovethe rim of the container 34. The position of a pair of pinch valvemembers 70, 71 with respect to a separation bag 1 and the tubes 4, 17,18 connected thereto when the separation bag 1 rests in the separationcell 40 associated with this pair of pinch valve members 70, 71 is shownin doted lines in FIGS. 1 and 2. Electric power is supplied to the pinchvalve members 70, 71 through a slip ring array 38 that is mounted arounda lower portion of the rotor shaft 32.

The separation apparatus further comprises four pairs of sensors 73, 74for monitoring the separation of the various components occurring withineach separation bag when the apparatus operates. Each pair of sensors73, 74 is embedded in the lid 47 of the container 41 of each separationcell 40 along the median longitudinal axis 42 of the container 41, afirst sensor 73 being located the farthest and a second sensor 74 beinglocated the closest to the rotation axis 31. When a separation bag 1rests in the container 41 and the lid 47 is closed, the first sensor 73(later the bag sensor) faces the upper triangular part of the separationbag 1 and the second sensor 74 (later the tube sensor) faces theproximal end of the first tube 4. The bag sensor 73 is able to detectblood cells in a liquid. The tube sensor 74 is able to detect thepresence of absence of liquid in the tube 4 as well as to detect bloodcells in a liquid. Each sensor 73, 74 may comprise a photocell includingan infrared LED and a photo-detector. Electric power is supplied to thesensors 73, 74 through the slip ring array 38 that is mounted around thelower portion of the rotor shaft 32.

The separation apparatus further comprises a first balancing means forinitially balancing the rotor when the weights of the four separationbags 1 contained in the separation cells 40 are different. The firstbalancing means substantially comprises the same structural elements asthe elements of the component transferring means described above,namely: four expandable hydraulic chambers 51 interconnected by aperipheral circular manifold 52, and a hydraulic liquid pumping station60 for pumping hydraulic liquid into the hydraulic chambers 51 through arotor duct 56, which is connected to the circular manifold 52. In orderto initially balance the rotor, whose four separation cells 40 containfour discrete volumes of a composite liquid that may not have the sameweight (because the four volumes may be not equal, and/or the density ofthe liquid may slightly differ from one volume to the other one), thepumping station 60 is controlled so as to pump into the interconnectedhydraulic chambers 51, at the onset of a separation process, apredetermined volume of hydraulic liquid that is so selected as tobalance the rotor in the most unbalanced situation. For whole blood, thedetermination of this balancing volume takes into account the maximumdifference in volume between two blood donations, and the maximumdifference in hematocrit (i.e. in density) between two blood donations.Under centrifugation forces, the hydraulic liquid will distributeunevenly in the four separation cells 40 depending on the difference inweight of the separation bags 1, and balance the rotor. In order to getan optimal initial balancing, the volume of the cavity 43 of theseparation cells 40 should be selected so that the cavities 43, whateverthe volume of the separation bags 1 contained therein, are not fullafter the determined amount of hydraulic liquid has been pumped into theinterconnected expansion chambers 51.

The separation apparatus further comprises a second balancing means, forbalancing the rotor when the weights of the components transferred intothe satellite bags 2, 3, 15 in the central container 34 are different.For example, when two blood donations have the same hematocrit anddifferent volumes, the volumes of plasma extracted from each donationare different, and the same is true when two blood donations have thesame volume and different hematocrit. As shown in FIGS. 4, 5, 6 thesecond balancing means comprises four flexible rectangular pouches 81,82, 83, 84 that are interconnected by four tube sections 85, 86, 87, 88,each tube section connecting two adjacent pouches by the bottom thereof.The pouches 81, 82, 83, 84 contain a volume of balancing liquid having adensity close to the density of the composite liquid. The volume ofbalancing liquid is so selected as to balance the rotor in the mostunbalanced situation. The four pouches 81, 82, 83, 84 are so dimensionedas to line the inner surface of the central container 34 and to have aninternal volume that is larger than the volume of balancing liquid sothat the balancing liquid can freely expand in any of the pouches 81,82, 83, 84. In operation, if, for example, four satellite bags 2respectively adjacent to the four pouches 81, 82, 83, 84 receivedifferent volumes of a plasma component, the four satellite bags 2 willpress unevenly, under centrifugation forces, against the four pouches81, 82, 83, 84, which will result in the balancing liquid becomingunevenly distributed in the four pouches 81, 82, 83, 84 and compensatingfor the difference in weight in the satellite bags 2.

The separation apparatus further comprises a controller 90 including acontrol unit (e.g. a microprocessor) and a memory unit for providing themicroprocessor with information and programmed instructions relative tovarious separation protocols (e.g. a protocol for the separation of aplasma component and a blood cell component, or a protocol for theseparation of a plasma component, a platelet component, and a red bloodcell component) and to the operation of the apparatus in accordance withsuch separation protocols. In particular, the microprocessor isprogrammed for receiving information relative to the centrifugationspeed(s) at which the rotor is to be rotated during the various stagesof a separation process (e.g. stage of component separation, stage of aplasma component expression, stage of suspension of platelets in aplasma fraction, stage of a platelet component expression, etc), andinformation relative to the various transfer flow rates at whichseparated components are to be transferred from the separation bag 1into the satellite bags 2, 3, 15. The information relative to thevarious transfer flow rates can be expressed, for example, as hydraulicliquid flow rates in the hydraulic circuit, or as rotation speeds of thestepper motor 64 of the hydraulic pumping station 60. The microprocessoris further programmed for receiving, directly or through the memory,information from the pressure gauge 68 and from the four pairs ofphotocells 73, 74 and for controlling the centrifuge motor 36, thestepper motor 64 of the pumping station 60, and the four pairs of pinchvalve members 70, 71 so as to cause the separation apparatus to operatealong a selected separation protocol.

Variants of the first embodiment of the separation apparatus describedabove are as follows:

Instead of the centralized hydraulic squeezing system described above, aseparation apparatus can be fitted with as many independent squeezingmeans as separation cells 40. An independent squeezing means may becomprised, for example, of a plate that can be moved by anyelectro-magnetic, electro-mechanical or hydraulic mechanism so as tosqueeze a separation bag against a wall of the cavity 43 of thecontainer 41 of a separation cell 40.

Instead of a system of interconnected hydraulic chambers or pouches, thefirst and/or second balancing means can comprise a ball balancerincluding a circular cage in which heavy balls can move freely. Thecircular cage is mounted on the rotor so as to be centered on therotation axis 31.

Instead of a central container 34 for containing all the satellite bags2, 3, 15 connected to the separation bags 1, a separation apparatus cancomprise as many satellite bag containers as separation cells. FIG. 9shows a container arrangement that can be used in such a separationapparatus. The container arrangement of FIG. 9 comprises a separationbag container 41 that is connected to or is made integral with asatellite bag container 54. The satellite bag container 54 comprises acavity 55 having the shape of a rectangular parallelepiped, whichcontains a pouch 81 of a balancing assembly as shown in FIG. 6. Theseparation bag container 41 is superimposed on the satellite bagcontainer 54 so that the openings of both containers are in the sameplane, facing the rotation axis 31 when the container arrangement ismounted on a rotor turntable 35.

The second sensors 74 can be embedded in the lids 47 of the containers41 so as to face an upper part of a separation bag 1 close to theconnection thereof to the first tube 4.

The diaphragm 50, instead of being secured to the container 41 so as toline a portion of the lower wall of the cavity 43, can be secured to thecontainer 41 so as to line a portion of the upper wall of the cavity 43.

In each separation cell 40, the hydraulic chamber 51, instead of beingdefined by a flexible diaphragm 50 lining the bottom wall of the cavity43 and a large portion of the lower wall of the cavity 43, can comprisea flexible pouch similar to a pouch of the second balancing means.

The second balancing means, instead of comprising four interconnectedpouches 81, 82, 83, 84 as shown in FIG. 6, can comprise a flexibletubular pouch 80 having two concentric walls as shown in FIG. 7. Thepouch 80 is so dimensioned as to line the inner surface of the centralcontainer 34 and to have an internal volume that is larger than thevolume of balancing liquid so that the balancing liquid can freelyexpand in one area of pouch or in another.

The pumping station 60, instead of a piston pump 61, 62, can compriseany pump (e.g. a positive displacement pump) whose output can becontrolled with sufficient accuracy.

FIGS. 10, 11, 12 show the rotor of a second embodiment of a separationapparatus for four discrete volumes of a composite liquid.

The rotor of this second embodiment essentially differs from the rotorof the embodiment of FIGS. 4 and 5 in the spatial arrangement of thepinch valve members 70, 71 and of the storage means for the satellitebags with respect to the separation cells 40. In this embodiment, thestorage means, instead of comprising a central container, comprises foursatellite containers 341, 342, 343, 344 that are arranged around acentral cylindrical cavity 340, in which the four pairs of pinch valvemember 70, 71 are mounted with their longitudinal axes parallel to therotation axis 31. The cavity 43 of a satellite container 341, 342, 343,344 has a regular bean-like cross-section, and a central longitudinalaxis that is parallel to the rotation axis 31 and intersects thelongitudinal axis 42 of the associated separation cell 40.

When a set of bag as shown in FIGS. 2, 3 a, 3 b is mounted on the rotorof FIGS. 11 to 12, the separation bag 1 and the satellite bags 2, 3, 15are located beyond the associated pinch valves members 70, 71 withrespect to the rotation axis 31. The tubes 4, 17, 18 and the three-wayconnector 16, 16 a, 16 b connecting the bags are then in the positionshown in FIGS. 2, 3 a, 3 b.

The operation of the separation apparatus of FIGS. 3 and 4, inaccordance to a first and second an illustrative separation protocols,will be described now.

According to a first separation protocol, four discrete volumes of bloodare separated into a plasma component, a first cell component comprisingplatelets, white blood cells, some red blood cells and a small volume ofplasma (later the “buffy coat” component) and a second cell componentmainly comprising red blood cells. Each volume of blood is contained ina separation bag 1 of a bag set represented in FIG. 2, in which it haspreviously been collected from a donor using the collection tube 5.After the blood collection, the collection tube 5 has been sealed andcut close to the separation bag. Typically, the volumes of blood are notthe same in the four separation bags 1, and the hematocrit varies fromone separation bag 1 to another one. Consequently, the separation bags 1have slightly different weights.

First Stage (First Protocol): Setting the Four Bag Sets in theSeparation Apparatus

Four separation bags 1 are loaded into the four separation cells 40. Thelids 47 are closed and locked, whereby the separation bags 1 are securedby their upper edge to the containers 41 (the pins 48 of the securingmeans pass then through the holes 8 in the upper corner of theseparation bags 1 and engage the recesses 49 or the securing means).

The tubes 17 connecting the separations bags 1 to the plasma componentbags 2, through the T connectors 16, are inserted in the groove 72 ofthe first pinch valve members 70. The tubes 18 connecting theseparations bags 1 to the buffy coat component bags 15, through the Tconnector 16, are inserted in the groove 72 of the second pinch valvemembers 71. The four plasma component bags 2, the four buffy coatcomponent bags 15, the four red blood cell component bags 3 and the fourleuko-reduction filters 13 are inserted in the central compartment 34 ofthe rotor. The four plasma component bags 2 are respectively placed indirect contact with the pouches 81 to 84 of the second balancing means.The pinch valve members 70, 71 are closed and the breakable stoppers 9in the tubes 4 connecting the separation bags 1 to the T connectors 16are manually broken.

Second Stage (First Protocol): Balancing the Rotor in Order toCompensate for the Difference In Weights of the Separation Bags

At the onset of the second stage, all the pinch valve members 70, 71 areclosed. The rotor is set in motion by the centrifuge motor 36 and itsrotation speed increases steadily until it rotates at a firstcentrifugation speed. The pumping station 60 is actuated so as to pump apredetermined overall volume of hydraulic liquid into the four hydraulicchambers 51, at a constant flow rate. This overall volume of liquid ispredetermined taking into account the maximum variation of weightbetween blood donations, so that, at the end of the second stage, theweights in the various separation cells 40 are substantially equal andthe rotor is substantially balanced, whatever the specific weights ofthe separation bags 1 that are loaded in the separation cells 40. Notethat this does not imply that the internal cavity 43 of the separationcells 40 should be filled up at the end of the balancing stage. For thepurpose of balancing the rotor, it suffices that there is enoughhydraulic liquid in the separation cells 40 for equalizing the weightstherein, and it does not matter if an empty space remains in eachseparation cell 40 (the size of this empty space essentially depends onthe volume of the internal cavity 43 of a separation cell 40 and theaverage volume of a blood donation). Because the hydraulic chambers 51are interconnected, the distribution of the overall volume of hydraulicliquid between the separations chambers 40 simply results from therotation of the rotor. When the weights of the separation bags 1 are thesame, the distribution of the hydraulic liquid is even. When they arenot, the distribution of the hydraulic liquid is uneven, and the smallerthe weight of a specific separation bag 1, the larger the volume of thehydraulic fluid in the associated hydraulic chamber 51.

Third Stage (First Protocol): the Blood within the Separation Bags 1 isSedimented to a Desired Level.

At the onset of this stage, all pinch valve members 70, 71 are closed.The rotor is rotated at a second centrifugation speed (highsedimentation speed or “hard spin”) for a predetermined period of timethat is so selected that, whatever the hematocrit of the blood in theseparation bags 1, the blood sediments in each of the separation bag 1at the end of the selected period to a point where the hematocrit of theouter red blood cell layer is about 90 and the inner plasma layer doesnot substantially contain anymore cells, the platelets and the whiteblood cells forming then an intermediary layer between the red bloodcell layer and the plasma layer.

Fourth Stage (First Protocol): a Plasma Component is Transferred intothe Plasma Component Bags 2.

At the onset of this stage, the rotation speed is decreased to a thirdcentrifugation speed, the four first pinch valve members 70 controllingaccess to the plasma component bags 2 are opened, and the pumpingstation 60 is actuated so as to pump hydraulic liquid at a firstconstant flow rate into the hydraulic chambers 51 and consequentlysqueeze the separation bags 1 and cause the transfer of plasma into theplasma component bags 2.

When blood cells are detected by the bag sensor 73 in the separationcell 40 in which this detection occurs first, the pumping station 60 isstopped and the corresponding first pinch valve member 70 is closed,either immediately of after a predetermined amount of time selected inview of the volume of plasma that it is desirable in the buffy coatcomponent to be expressed in a next stage.

Following the closure of the first (first) pinch valve member 70 (i.e.the first pinch valve of the group of first pinch valve members 70) toclose, the pumping station 60 is actuated anew so as to pump hydraulicliquid at a second, lower, flow rate into the hydraulic chambers 51 andconsequently squeeze the three separation bags 1 whose outlet is notclosed by the corresponding first pinch valve members 70.

When blood cells are detected by the bag sensor 73 in the separationcell 40 in which this detection occurs second, the pumping station 60 isstopped and the corresponding first pinch valve member 70 is closed(same timing as for the closing of the first (first) pinch valve memberto close).

Following the closure of the second (first) pinch valve member 70 toclose, the pumping station 60 is actuated anew so as to pump hydraulicliquid at the second flow rate into the hydraulic chambers 51 andconsequently squeeze the two separation bags 1 whose outlet is notclosed by the corresponding first pinch valve members 70.

When blood cells are detected by the bag sensor 73 in the separationcell 40 in which this detection occurs third, the pumping station 60 isstopped and the corresponding first pinch valve member 70 is closed(same timing as for the closing of the first (first) pinch valve memberto close).

Following the closure of the third (first) pinch valve member 70 toclose, the pumping station 60 is actuated anew so as to pump hydraulicliquid at the second flow rate into the hydraulic chambers 51 andconsequently squeeze the separation bag 1 whose outlet is not yet closedby the corresponding first pinch valve member 70.

When blood cells are detected by the bag sensor 73 in the separationcell 40 in which this detection occurs last, the pumping station 60 isstopped and the corresponding first pinch valve member 70 is closed(same timing as for the closing of the first pinch valve member toclose).

In the plasma component transfer process described above, the transferof the four plasma components starts at the same time, run in partsimultaneously and stop independently of each other upon the occurrenceof a specific event in each separation bag (detection of blood cells bythe bag sensor).

As a variant, when the second flow rate is sufficiently low and theclosing of the first pinch valve member 70 occurs almost simultaneouslywith the detection of blood cells in the separation bags, then thepumping station can be continuously actuated during the fourth stage.

The fourth stage ends when the four first pinch valve members 70 areclosed.

Fifth Stage (First Protocol): a Buffy Coat Component is Transferred intothe Buffy Coat Component Bags 15.

The control unit 90 is programmed to start the fifth stage after thefour first pinch valve members 70 are closed, upon receiving informationfrom the last bag sensor 73 to detect blood cells.

At the onset of this stage, the rotation speed remains the same (thirdcentrifugation speed), a first of the four second pinch valve members 71controlling access to the buffy coat component bags 15 is opened, andthe pumping station 60 is actuated so as to pump hydraulic liquid at athird constant flow rate into the hydraulic chambers 51 and consequentlysqueeze the separation bag 1 in the separation cell 40 associated withthe opened second pinch valve members 71 and cause the transfer of thebuffy coat component into the buffy coat component bag 2 connected tothis separation bag 1.

After a predetermined period of time after blood cells are detected bythe tube sensor 74 in the separation cell 40 associated with the openedsecond pinch valve member 71, the pumping station 60 is stopped and thesecond pinch valve member 71 is closed.

After the first (second) pinch valve member 71 has closed (i.e. thefirst pinch valve of the group of second pinch valve members 71), asecond (second) pinch valve member 71 is opened, and a second buffy coatcomponent is transferred into a buffy coat component bag 2, in the sameway as above.

The same process is successively carried out to transfer the buffy coatcomponent from the two remaining separation bags 1 into the buffy coatcomponent bag 2 connected thereto.

In the buffy coat component transfer process described above, thetransfers of the four buffy coat components are successive, and theorder of succession is predetermined. However, each of the second, thirdand four transfers starts following the occurrence of a specific eventat the end of the previous transfer (detection of blood cells by thetube sensor 74 or closing of the second valve member 71).

As a variant, when the third flow rate is sufficiently low and theclosing of the second pinch valve members 71 occurs almostsimultaneously with the detection of blood cells in the tubes 4, thenthe pumping station can be actuated continuously during the fourthstage.

As a variant, the control unit 90 is programmed to start the fifth stageafter a predetermined period of time after receiving information fromthe first (or the second or the third) bag sensor 73 to detect bloodcells. The period of time is statistically or empirically determined sothat, whatever the event from which it starts running (detection of theblood cells by either one of the first, second, and third bag sensor 73to detect blood cells), the four first pinch valve members 70 are closedwhen it is over.

The fifth stage ends when the four second pinch valve members 71 areclosed.

Sixth Stage (First Protocol): the Centrifugation Process is Ended.

The control unit 90 is programmed to start the sixth stage after thefour (second) pinch valve members 71 are closed, upon receivinginformation from the last tube sensor 74 to detect blood cells.

The rotation speed of the rotor is decreased until the rotor stops, thepumping station 60 is actuated so as to pump the hydraulic liquid fromthe hydraulic chambers 51 at a high flow rate until the hydraulicchambers 51 are empty, and the first and second pinch valve members 70,71 are actuated so as to seal and cut the tubes 17, 18. The blood cellsremain in the separation bags 1.

When the fifth stage is completed, the four bag sets are removed fromthe separation apparatus and each bag set is separately handledmanually.

The breakable stopper 10 blocking the communication between theseparation bag 1 and the tube 6 connected thereto is broken, as well asthe breakable stopper 14 blocking the communication between the secondsatellite bag 3 and the tube 6. The storage solution contained in thesecond satellite bag 3 is allowed to flow by gravity through theleuko-reduction filter 13 and into the separation bag 1, where it ismixed with the red blood cells so as to lower the viscosity thereof. Thecontent of the separation bag 1 is then allowed to flow by gravitythrough the filter 13 and into the second satellite bag 3. The whiteblood cells are trapped by the filter 13, so that substantially only redblood cells are collected into the second satellite bag 3.

As a variant, the control unit 90 is programmed to start the sixth stageafter a predetermined period of time after receiving information fromthe first (or the second or the third) tube sensor 74 to detect bloodcells. The period of time is statistically or empirically determined sothat, whatever the event from which it starts running (detection of theblood cells by either one of the first, second, and third tube sensor 74to detect blood cells), the four second pinch valve members 71 areclosed when it is over.

According to a second separation protocol, four discrete volumes ofblood are separated into a plasma component, a platelet component and ared blood cell component. Each volume of blood is contained in aseparation bag 1 of a bag set represented in FIG. 2, in which it haspreviously been collected from a donor using the collection tube 5.After the blood collection, the collection tube 5 has been sealed andcut close to the separation bag 1. Typically, the volumes of blood arenot the same in the four separation bags 1, which, consequently, haveslightly different weights. Also, typically, the hematocrit varies fromone separation bag 1 to another one.

First stage (second protocol): setting the four bag sets in theseparation apparatus

This stage is identical to the first stage of the first protocol.

Second stage (second protocol): balancing the rotor in order tocompensate for the difference in weights of the separation bags

This stage is identical to the second stage of the first protocol.

Third stage (second protocol): the blood within the separation bags 1 issedimented to a desired level.

This stage is identical to the third stage of the first protocol.

Fourth stage (second protocol): a first, larger, portion of plasma istransferred into the plasma bags 2, while a second, smaller, portion ofplasma remains in the separation bags 1.

This stage is substantially the same as the fourth stage of the firstprotocol. However, the expression of plasma from each separation bag 1into the attached plasma component bag 2 is stopped immediately afterdetection of blood cells by the corresponding bag sensor 73, so that thevolume of plasma remaining in the separation bag 1 is large enough toallow the platelets to be re-suspended therein.

Fifth stage (second protocol): a platelet component is prepared in theseparation bag 1.

At the onset of this fifth stage, the first and second valve members 70,71 are closed. The rotor is stopped and the pumping station 60 isactuated so as to pump a volume of hydraulic liquid from the hydraulicchambers 51 at a high flow rate. The rotor is then controlled so as tooscillate back and forth around the rotation axis 31 for a determinedperiod of time, at the end of which the cells in the separation bags 1are substantially suspended in plasma. The rotor is then set in motionagain by the centrifuge motor 36 so that its rotation speed increasessteadily until it reaches a fourth centrifugation speed (lowsedimentation speed or “soft spin”). The rotor is rotated at the fourthrotation speed for a predetermined period of time that is selected sothat the blood sediments in the separation bags 1 at the end of theselected period to a point where the separation bags 1 exhibit an outerlayer comprising packed red blood cells and an inner annular layersubstantially comprising platelets suspended in plasma.

Sixth stage (second protocol): a platelet component is transferred intothe platelet bags 15.

This stage is substantially the same as the fifth stage of the firstprotocol (buffy coat expression).

Seventh stage (second protocol): the centrifugation process is ended.

This stage is substantially the same as the sixth stage of the firstprotocol.

FIGS. 13 to 18 show a third embodiment of a separation apparatus forfour discrete volumes of a composite liquid.

The separation apparatus of FIG. 13 to 18 is particularly adapted to theseparation of a composite fluid in two components, for example theseparation of whole blood into a cell component (red blood cells, whitecells and platelets) and a plasma component substantially devoid ofcells or the separation of whole blood into a cell component (red bloodcells, white cells and a small amount of platelets) and a plasmacomponent containing a large amount of platelets in suspension.

The main differences between the first separation apparatus shown inFIGS. 4 and 5 and the third separation apparatus shown in FIGS. 13 to 18are as follows:

-   -   The shape of the separation cells 100 of the third separation        apparatus is different from the shape of the separation cells 40        of the first separation apparatus.    -   Each of the separation cells 100 of the third separation        apparatus is associated with one pinch valve member 70 and one        tube sensor 74.    -   The third separation apparatus does not comprise a pumping        station for pumping a hydraulic liquid in and out of the        hydraulic chambers of the separation cells 100.

In more details, a separation cell 100 for the third separationapparatus comprises a container 101 having the general shape of arectangular parallelepiped. The cavity (also referred to as the“separation compartment”) of the container 101, which has also thegeneral shape of a rectangular parallelepiped, is so dimensioned as toloosely accommodate a separation bag 1 full of liquid, of the type shownin FIG. 2. The separation cell 100 further comprises an elasticdiaphragm 110, which defines within the cavity of the container 101 afirst chamber 102 for receiving a separation bag 1, and a secondhydraulic chamber 103 that is connected to the peripheral manifold 52,through an inlet aperture 104 close to the bottom of the container 101.The separation cell 100 further comprises a lid having two flaps 105,106 that are hinged to the longer parallel sides of the opening of thecontainer 101. The two flaps 105, 106 can be locked in a closed positionby a locking means (not shown). The separation cell 100 furthercomprises a securing means for securing a separation bag 1 within theseparation cell 100. The bag securing means comprises two pins 107 andtwo corresponding recesses 108 that respectively protrude or open on theedges of the flaps 105, 106 that face each other when the lid is closed.The two pins 107 are so spaced apart and dimensioned as to fit into thetwo holes 8 in the upper corner of a separation bag 1. The two flaps105, 106 also comprise on their facing edges three semi-cylindricalholes 109 for accommodating the proximal end of three tubes 4, 5, 6embedded in the upper area of a separation bag 1. The outer flap 106includes a cavity facing the median semi-cylindrical hole 109, forcontaining the bag sensor 74.

As shown in FIGS. 15 to 18, the diaphragm 110 comprises a flatrectangular socket 111 almost as wide as a separation cell 100. Thediaphragm 110 further comprises a large, rectangular, connecting portion112 extending around the mouth of the socket 111, perpendicularly to thesocket 111 when the diaphragm 110 is not deformed by a separation bag 1and it is held in an upright position (FIG. 15). The socket 111 isconnected to the connecting portion 112 along the longitudinal medianaxis thereof. The connecting portion 112 has a surface slightly largerthan a transversal cross-section of the cavity of the container 101. Thediaphragm 110 is tightly attached to the top of the container 101 by aperipheral area of the connecting portion 112. The diaphragm 110 is madeof an elastic and deformable elastomeric material so selected that thediaphragm 110 conforms very closely the shape of a separation bag 1before and during centrifugation and as shown in FIGS. 16 to 18.

As mentioned above, the separation apparatus shown in FIG. 13 does notcomprise a pumping station for pumping a hydraulic fluid in and out ofthe hydraulic chambers 103. Instead, it comprises a reservoir 120 forhydraulic liquid, which is fixed with respect to the rotor, and which isdirectly connected to the rotor duct 56 by a conduit 121 and a rotaryseal 122. The conduit 121 is fitted with a valve 123. The reservoir 120is secured to a frame of the separation apparatus so as to be lower thanthe four separation cells 100. When the separation apparatus is used forseparating red blood cells from plasma (with or without suspendedplatelets), the density of the hydraulic liquid is selected, for reasonsexplained below, so as to be between the density of packed red bloodcells and the density of plasma.

The component transferring means of the third separation apparatusessentially comprises the reservoir 120 that is directly connected tothe rotor duct 56 by the rotary seal 122, the hydraulic chambers 103,and the motor 36 that drives the rotor in rotation. When the valve 123is opened and the rotation speed of the rotor reaches a determinedthreshold, which depends on the height between the reservoir 120 and theseparation cells 100 and the distance between the rotation axis 31 andthe separation cells 100, then the hydraulic liquid flows from thereservoir 120 into the hydraulic chambers 103 so as to fill up thehydraulic chamber 103 and squeeze the separation bags 1 therein,whatever the volume/weight of the separation bags 1. The speed thresholdis substantially below the rotation speed at which the rotor is rotatedfor separating blood components (“high spin” as well as “soft spin). Thetransfer of a separated component from a separation bag 1 into asatellite bag 2 is then controlled by the opening/closing of the pinchvalve member 70 in which the tube 4 connecting the two bags is inserted.

The first balancing means of the third separation apparatus essentiallycomprises the reservoir 120 that is directly connected to the rotor duct56 through the rotary seal 122, the hydraulic chambers 103, the motor 36that drives the rotor in rotation, and the valve 123. At the onset of aseparation process, the valve 123 is opened for a predetermined periodof time so as to allow the transfer, in the interconnected hydraulicchambers 103, of a predetermined volume of hydraulic liquid that is soselected as to balance the rotor in the most unbalanced situation. Forwhole blood, the determination of this balancing volume takes intoaccount the maximum difference in volume between two blood donations,and the maximum difference in hematocrit (i.e. in density) between twoblood donations.

A variant of the third embodiment of a separation apparatus does notcomprise a valve 123 on the conduit 121 connecting the reservoir 120 tothe rotor duct 56. As a result, when the threshold speed is reached, thehydraulic liquid is pumped from the reservoir 120 into the hydraulicchambers 103 until the pressure that is building up within theseparation cells 100 prevents further pumping. The filling up of thespace available in the separation cells 100 with hydraulic liquid mightnot however result in an optimal balance of the rotor depending, inparticular, on the difference in weight of the separation bags 1, oftheir volume, and of the density of the hydraulic liquid.

The operation of the third separation apparatus, in accordance to athird illustrative separation protocol, will be described now.

According to a third separation protocol, four discrete volumes of bloodare separated into a plasma component (including or not including asubstantial amount of platelets) and a blood cell component (includingplatelets, or residual platelets, white blood cells and red bloodcells). Each volume of blood is contained in a separation bag 1 of a bagset represented in FIG. 1, in which it has previously been collectedfrom a donor using the collection tube 5. After the blood collection,the collection tube 5 has been sealed and cut close to the separationbag 1. Typically, the volumes of blood are not the same in the fourseparation bags 1 and the hematocrit varies from one separation bag 1 toanother one. As a result, the separation bags have slightly differentweights.

First Stage (Third Protocol): Setting the Four Bag Sets in theSeparation Apparatus

Four separation bags 1 are inserted into the socket 111 of a diaphragm110 within the four separation cells 100 as shown in FIG. 16. The twoflaps 105, 106 of the lids of the separation cells 100 are closed andconsequently secure the top of the separation bags 1 to the separationcells 100. The tube sensors 74 embedded in the outer flap 106 of thelids now face the proximal end of the tubes 4 connecting the separationbags 1 to the plasma component bags 2. The tubes 4 are inserted in thegroove 72 of the pinch valve members 70. The four plasma component bags2, the four red blood cell component bags 3 and the four leuko-reductionfilters 13 are inserted in the central compartment 34 of the rotor. Thepinch valve members 70 are closed and the breakable stoppers 9 in thetubes 4 connected to the plasma component bags 2 are manually broken.

Second Stage (Third Protocol): Balancing the Rotor in Order toCompensate for the Difference In Weights of the Separation Bags

At the onset of this second stage, the pinch valve members 70, in whichthe tubes 4 are engaged, are closed. The valve 123 on the conduitconnecting the reservoir 120 to the rotor duct 56 is opened. The rotoris set in motion by the centrifuge motor 36 and its rotation speedincreases steadily until it rotates at a predetermined sedimentationspeed. Before it rotates at the sedimentation speed, the rotor reaches athreshold speed at which its rotation causes the pumping of hydraulicliquid from the reservoir 120 into the interconnected hydraulic chambers103 of the separation cells 100. The valve is closed 123 after apredetermined amount of hydraulic fluid sufficient for balancing therotor has been transferred in the hydraulic chambers 103. Because thehydraulic chambers 103 are interconnected by the peripheral manifold 52,the hydraulic liquid gets automatically distributed in the separationcells 100 so as to balance the rotor. When the weights of the separationbags 1 are the same, the distribution of the hydraulic liquid is even.When they are not, the distribution of the hydraulic liquid is uneven,and the smaller the weight of blood in a specific separation bag 1, thelarger the volume of the hydraulic fluid in the associated hydraulicchamber 103.

Third Stage (Third Protocol): the Blood within the Separation Bags 1 isSedimented to a Desired Level.

When it is desired to separate a plasma component containing a largeamount of suspended platelets (“platelet rich plasma”) and a cellcomponent mainly containing red blood cells and white blood cells, therotor is rotated at a first sedimentation speed (about 2000 RPM, usuallyreferred to as “soft spin”).

When it is desired to separate a plasma component substantially devoidof cells (“platelet poor plasma”) and a cell component containing redblood cells, white blood cells and platelets, the rotor is rotated at asecond sedimentation speed (about 3200 RPM, usually referred to as “hardspin”).

The rotor is rotated at the selected sedimentation speed for apredetermined period of time that is selected so that, whatever thehematocrit of the blood in the separation bags 1, the blood sediments atthe desired level in each of the separation bag 1 at the end of theselected period. Since, as mentioned above, the density of the hydraulicliquid is selected so as to be between the density of the packed redcells and the density of the plasma, the separation bag 1 will take ahour-glass shape at the end of the sedimentation stage, as shown in FIG.17.

Fourth Stage (Third Protocol): a Plasma Component is Transferred intothe Satellite Bags 2.

At the onset of this stage, the four pinch valve members 70 controllingthe access to the plasma component bags 2 are opened. This causes adecrease in pressure within the separation cells 100 and hydraulicliquid starts flowing again into the hydraulic chambers 103. The raisingvolume of hydraulic fluid in the hydraulic chamber 103 squeezes theseparation bags 1 and causes the transfer of the plasma component intothe first satellite bags 2. Because the hydraulic liquid has a lowerdensity than the density of the packed red blood cells, the red bloodcells remain at the bottom of the separation cell 100 and the separationbags 1 progressively collapse above the red cells as shown in FIG. 18.

When each tube sensor 74 detects blood cells, then the associated pinchvalve member 70 is closed. When the volumes of blood in the fourseparation bags 1 are different, and/or the hematocrit of the blood inthe four separation bags 1 is different (which will be generally thecase), then the four pinch valve members 70 close one after the other.

The fourth stage end when the four pinch valve members 70 are closed.

Fifth Stage (Third Protocol): the Centrifugation Process is Ended.

When the last pinch valve member 70 closes, the rotation speed of therotor is decreased until the rotor stops. The hydraulic liquidsimultaneously drains from the hydraulic chambers 103 into the reservoir120. The red blood cells and the white blood cells remain in theseparation bag 1 (as well as the platelets when the plasma componentcollected is a “platelet poor plasma”).

When the fifth stage is completed, the four bag sets are removed fromthe separation apparatus and each bag set is separately handledmanually.

The breakable stopper 10 blocking the communication between theseparation bag 1 and the tube 6 connected thereto is broken, as well asthe breakable stopper 14 blocking the communication between the secondsatellite bag 3 and the tube 6. The storage solution contained in thesecond satellite bag 3 is allowed to flow by gravity through the filter13 and into the separation bag 1, where it is mixed with the blood cellsso as to lower the viscosity thereof. The content of the separation bag1 is then allowed to flow by gravity through the filter 13 and into thesecond satellite bag 3. The white blood cells and the platelets aretrapped by the filter 13, so that substantially only red blood cells arecollected into the second satellite bag 3.

FIG. 19 shows a fourth embodiment of a separation apparatus for fourdiscrete volumes of a composite liquid.

The main differences between the third separation apparatus shown inFIGS. 13 to 18 and the fourth separation apparatus shown in FIG. 19 areas follows:

-   -   The fourth separation apparatus does not comprise a fixed        reservoir directly connected to the separation chambers, via a        conduit, a rotary seal and a rotor duct;    -   The fourth separation apparatus comprises a hydraulic liquid        reservoir 130 that is mounted on the rotor.

The rotor of the apparatus of FIG. 19 comprises:

-   -   A central container 34 for satellite bags, having the shape of a        cylindrical bucket;    -   A turntable 35 having a frusto-conical wall supporting four        separation cells 100 at an angle with respect to the rotation        axis 31; the turntable 35 is connected by its smaller diameter        section to an upper rim of the central container 34 so as to        flare underneath the rim of the central container 34;    -   A reservoir 130 for hydraulic liquid, which comprises a circular        bottom wall 131 and frusto-conical wall 132 connected by its        smaller diameter section to the circular bottom wall 131 and by        its larger diameter section to the lower rim of the turntable 35        (i.e. the section of the turntable having the larger diameter).        In other words, the interior of the reservoir 130 has a complex        geometrical volume that is symmetrical with respect to the        rotation axis 31 and that is defined by the outside surface or        the central container 34, the inner surface of the turntable 35,        the inner surface of the frusto-conical wall 132 of the        reservoir, and the inner surface of the bottom wall 131 of the        reservoir.    -   A rotor shaft 32, which is connected to the bottom wall of the        reservoir 130.

The reservoir 130 is fluidly connected to the hydraulic chamber 103 ofeach separation cell 100 by an outlet aperture 133 through the turntable35 that coincides with the inlet aperture 104 of the hydraulic chambers103. As shown, the outlet apertures 133 are located the farthest fromthe rotation axis 31. With this arrangement, the hydraulic liquid flowsfrom the reservoir 130 into the hydraulic chambers 103 of the separationcells 100 under centrifugal forces as soon as the rotor starts rotating.When the separation apparatus is to be used for separating red bloodcells from plasma (with or without suspended platelets), the density ofthe hydraulic fluid is selected so as to be between the density of packred cells and the density of plasma.

In this fourth embodiment of a separation apparatus, the componenttransferring means essentially comprise the reservoir 130, the hydraulicchambers 103 and the motor 36 that drives the rotor in rotation. Whenthe rotor rotates, the hydraulic liquid drains from the reservoir 130into the hydraulic chambers 103 under centrifugal forces and presses theseparation bags 1 within the separation cell 100 through the elasticdiaphragm 110. The transfer of a separated component from a separationbag 1 into a satellite bag 2 is controlled by the opening/closing of thepinch valve member 70 in which the tube 4 connecting the two bags isinserted.

The first balancing means essentially comprise the reservoir 130, thehydraulic chambers 103 and the motor 36 that drives the rotor inrotation. As soon as the rotor starts rotating, hydraulic fluid flowsfrom the reservoir 130 into the hydraulic chambers 103 until itcompletely fills up the space let vacant in the separation cells 100 bythe separation bags 1, which happens before the rotor has reach thedesired sedimentation speed. The filling up of the space available inthe separation cells 100 with hydraulic liquid might not however resultin an optimal balance of the rotor depending, in particular, on thedifference in weight of the separation bags 1, on their volume, and onthe density of the hydraulic liquid.

It will be apparent to those skilled in the art that variousmodifications can be made to the apparatus and method described herein.Thus, it should be understood that the invention is not limited to thesubject matter discussed in the specification. Rather, the presentinvention is intended to cover modifications and variations.

1. An apparatus for separating at least two discrete volumes of acomposite liquid into at least a first component and a second component,whereby the at least two discrete volumes can have different weights,the apparatus comprising a centrifuge comprising: a rotor having arotation axis, comprising at least two separation cells, each forcontaining a separation bag containing a volume of composite liquid; anda first balancing means for balancing the rotor when the respectiveweights of the at least two separation bags in the at least twoseparation cells are different, comprising: at least two expandablehydraulic chambers within the at least two separation cellsrespectively, wherein the at least two hydraulic chambers are fluidlyinterconnected; a source of hydraulic liquid fluidly connected to the atleast two hydraulic chambers; a liquid transferring means fortransferring a volume of hydraulic liquid from the hydraulic liquidsource into the at least two interconnected hydraulic chambers so as tosubstantially balance the rotor when two separation bags respectivelycontained in the at least two different separation cells have differentweights; a storage means included in the rotor for storing at least twosatellite bags respectively connected to at least two separation bagscontained in the at least two separation cells; and a componenttransferring means for transferring at least one separated componentfrom each separation bag into a satellite bag connected thereto.
 2. Anapparatus according to claim 1, further comprising a control unitprogrammed for causing the liquid transferring means to transfer apredetermined volume of hydraulic liquid from the hydraulic liquidsource into the at least two interconnected hydraulic chambers, whereinthe predetermined volume of hydraulic liquid is selected so as tosubstantially balance the rotor whatever the weights of two separationbags respectively contained in the at least two different separationcells.
 3. An apparatus according to claim 1, wherein the liquidtransferring means comprises a pumping means for pumping a volume ofhydraulic fluid into the at least two interconnected hydraulic chambers.4. An apparatus according to claim 1, wherein the at least two hydraulicchambers are interconnected by a circular conduit centered on therotation axis, and the circular conduit is connected to each hydraulicchamber to an area thereof that is closer to a periphery of the rotorthan to the rotation axis.
 5. An apparatus according to claim 1, whereinthe component transferring means comprises a pumping means for pumpinghydraulic liquid from the source of hydraulic liquid into the at leasttwo interconnected hydraulic chambers so as to squeeze the at least twoseparation bags within the at least two separation cells and to cause acomponent separated therein to flow into a satellite bag connected toeach separation bag.
 6. An apparatus according to claim 1, furthercomprising a second balancing means for balancing the rotor when the atleast two satellite bags stored in the storage means cause an unbalanceof the rotor.
 7. An apparatus according to claim 6, wherein: the storagemeans comprises a central container, around which the at least twoseparation cells are symmetrically arranged with respect to the rotationaxis; and the second balancing means comprises at least twointerconnected flexible pouches partially filled with a liquid, whereinthe pouches are arranged against a wall of the central container so thatthe at least one satellite bag connected to each separation bag pressesonto a pouch during centrifugation.
 8. An apparatus according to claim6, wherein: the storage means comprises a central container, aroundwhich the at least two separation cells are symmetrically arranged withrespect to the rotation axis; and the second balancing means comprises acylindrical flexible pouch partially filled with a liquid lining a wallof the central container so that the at least one satellite bagconnected to each separation bag presses onto the pouch duringcentrifugation.
 9. An apparatus according to claim 6, wherein: thestorage means comprises one container associated with each separationcell, the container being located between the separation cell and therotation axis; and the second balancing means comprises one flexiblepouch partially filled with a liquid arranged against a wall of eachcontainer so that a satellite bag stored in the container presses onto apouch during centrifugation, wherein a flexible pouch in one containeris fluidly interconnected with a pouch in another container.
 10. Anapparatus according to claim 1 , further comprising: at least one valvemember associated with each separation cell for selectively allowing orblocking a flow of fluid between a separation bag and a first satellitebag, wherein the at least one valve member is mounted on the rotor so asto be between the associated separation cell and the storage means, withrespect to the rotation axis.
 11. An apparatus according to claim 1,further comprising: at least one valve member associated with eachseparation cell for selectively allowing or blocking a flow of fluidbetween a separation bag and a first satellite bag, wherein the at leastone valve member is mounted on the rotor so that the storage means isbetween the at least one valve member and the associated separationcell, with respect to the rotation axis.
 12. An apparatus according toclaims 1, further comprising at least one sensor associated with eachseparation cell for generating information related to a characteristicof a component separated in a separation bag within the separation cell.13. An apparatus according to claim 12, wherein the at least one sensoris mounted on the rotor so as to detect a characteristic of a componentin a separation bag contained in the associated separation cell.
 14. Anapparatus according to claim 12, wherein the at least one sensor ismounted on the rotor so as to detect a characteristic of a component ina tube connected to a separation bag contained in the associatedseparation cell.
 15. An apparatus according to claim 1, wherein eachseparation cell comprises a substantially closed cavity having alongitudinal axis intersecting the rotation axis of the rotor andcomprising a portion closer to the rotation axis of the rotor that isdefined by four walls converging towards the longitudinal axis of thecavity.
 16. An apparatus according to claim 15, wherein the longitudinalaxis of the cavity of each separation cell intersects the rotation axisof the rotor at an acute angle.
 17. An apparatus according to claim 1,wherein each separation cell comprises a cavity having a bottom wall, anupper wall and a lower wall, and the hydraulic chamber is underneath amembrane that is lining at least part of either the upper wall or thelower wall of the cavity.
 18. An apparatus according to claim 17,wherein the density of the hydraulic liquid is so selected as to behigher than the density of the component having the highest density. 19.An apparatus according to claim 1, wherein each separation cellcomprises a cavity having a bottom wall, an upper wall, and a lowerwall, and the hydraulic chamber comprising a flexible pouch that restsat least on part the lower wall.
 20. An apparatus according to claim 1,wherein each separation cell comprises a securing means for securing anupper edge of a separation bag so that the upper edge is the portion ofthe separation bag that is the closest to the rotation axis.
 21. Anapparatus according to claim 1, further comprising: at least one sensorassociated with each separation cell for generating information relatedto a characteristic of a component separated in a separation bag withinthe separation cell; a memory unit for storing at least one change inrotation speed of the rotor; and a control unit programmed: forreceiving from the memory the at least one change in rotation speed, andinformation generated by the at least one sensor associated with eachseparation cell; and for causing the at least one change in rotationspeed in view of information generated by one of the at least one sensorassociated with each of the at least two separation cells.
 22. Anapparatus according to claim 21, wherein the control unit is programmedfor causing the at least one change of rotation speed in view ofinformation generated by the first of the at least one sensor associatedwith the at least two separation cells that detects a characteristic ofa component separated in a separation bag within a separation cell. 23.An apparatus according to claim 21, wherein the control unit isprogrammed for causing the at least one change of rotation speed in viewof information generated by the last of the at least one sensorassociated with the at least two separation cells that detects acharacteristic of a component separated in a separation bag within aseparation cell.
 24. An apparatus according to claim 21, furthercomprising at least one valve member associated with each separationcell for selectively allowing or blocking a flow of fluid between aseparation bag within the separation cell and a satellite bag connectedthereto, wherein the control unit is further programmed for causing atleast once in a separation process the at least one valve memberassociated with a separation cell to block a flow of fluid between aseparation bag within the separation cell and a satellite bag connectedthereto following a detection of the characteristic of a separatedcomponent by the at least one sensor associated with the same separationcell.
 25. An apparatus according to claim 21, further comprising atleast one valve member associated with each separation cell forselectively allowing or blocking a flow of fluid between a separationbag within the separation cell and a satellite bag connected thereto,wherein the control unit is further programmed for causing at least oncein a separation process the at least one valve member associated with aseparation cell to allow a flow of fluid between a separation bag withinthe separation cell and a satellite bag connected thereto following adetection of the characteristic of a separated component by the at leastone sensor associated with another separation cell.
 26. An apparatusaccording to claim 21, further comprising at least one valve memberassociated with each separation cell for selectively allowing orblocking a flow of fluid between a separation bag within the separationcell and a satellite bag connected thereto, wherein the control unit isfurther programmed for: causing the rotor to rotate at a sedimentationspeed for separating a least two components in at least two separationbags contained in the at least two separation cell respectively; causingthe least one valve member associated with each separation cell to allowa flow of fluid between each separation bag and the satellite bagconnected thereto; causing the component transferring means to transferat least a portion of a separated component from each of the at leasttwo separation bags into the satellite bag connected thereto; causingthe least one valve member associated with each separation cell to blocka flow of fluid between the separation bag within the separation celland the satellite bag connected thereto, when the sensor associated withthe separation cell detects the characteristic of a separated component.27. An apparatus according to claim 26, wherein the control unit isfurther programmed for: causing the component transferring means to stoptransferring a separated component from the at least two separation bagsinto the satellite bags connected thereto when one sensor associatedwith one of the at least two the separation cells detects thecharacteristic of a separated component; causing the componenttransferring means to transfer a separated component from the at leasttwo separation bags into the satellite bags connected thereto, after thevalve member associated with the separation cell associated with thesensor that has detected the characteristic of a separated component hasblocked a flow of fluid between the separation bag and the satellite bagconnected thereto.
 28. An apparatus according to claim 26, wherein: theat least one sensor comprises a first sensor for detecting acharacteristic of a separated component in a separation bag within aseparation cell; the least one valve member comprises a first valvemember for allowing or blocking a flow of fluid between a separation bagand a first satellite bag connected thereto; the control unit is furtherprogrammed for controlling an actuation of the first valve member inview of information from the first sensor.
 29. An apparatus according toclaim 28, wherein: the at least one sensor comprises a second sensor fordetecting a characteristic of a separated component in a tube connectinga separation bag to a second satellite bag; the least one valve membercomprises a second valve member for allowing or blocking a flow of fluidbetween a separation bag and a second satellite bag connected thereto;the control unit is further programmed for controlling an actuation of asecond valve member in view of information from the second sensor.